Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials.

OBJECTIVE: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. DESIGN: Pooled analyses of data from four double-blinded, randomized controlled trials. PARTICIPANTS: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. MEASUREMENTS: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). RESULTS: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (-0.4 ± 2.6 kg; all P < 0.01 vs placebo). CONCLUSIONS: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

Sex differences in the association of Framingham Cardiac Risk Score with cognitive decline in community-dwelling elders without clinical heart disease.

OBJECTIVE: To investigate a possible link between cardiovascular risk factors and age-related cognitive decline, the association of the 1998 Framingham Cardiac Risk Score (FCRS) with the trajectory of cognitive function test (CFT) performance over an 18 year period was examined in adults 50 years and older without clinical heart disease at baseline. METHODS: Participants were 985 men and women who had assessments of cognitive function at 3- to 4-year intervals. The association of FCRS category with CFT score trajectory was examined using mixed-effects models stratified by sex and controlling for age, educational level, and number of successive cognitive assessments. RESULTS: At baseline, median FCRS corresponded to a 14% risk of a coronary heart disease event within 10 years for men and an 8% risk for women; 31% of men and 6% of women were at high (>20%) risk. In longitudinal analyses, women with FCRS risk higher than 7% had a higher rate of decline on tests of verbal fluency (p values < .05) and long-term recall (p values < .01) compared with low-risk women; modest, but significant (p values < .05), differences in the trajectory of Mini-Mental State Examination and Trail-Making Test B scores were also apparent. FCRS category was not related to the rate of decline in CFT performance in men. CONCLUSIONS: For older women, very low levels of risk of coronary heart disease were associated with preservation of cognitive function for 10 years, suggesting that the maintenance of cardiovascular health may slow cognitive decline. The minimal association in men, who were at higher baseline risk, may be due to the selective attrition of men with greater cognitive decline.

Does leptin predict incident hypertension in older adults?

OBJECTIVE: Leptin is associated with blood pressure (BP) in experimental and cross-sectional studies, but only one previous prospective study of middle-aged men has reported the association between leptin and incident hypertension. We examined the association of leptin levels with incident hypertension in a population-based study of older men and women. DESIGN: Longitudinal cohort study. POPULATION: Participants were 602 community-dwelling older adults with normal baseline BP levels who attended a research clinic visit between 1984 and 1987 and again 4.4 years later (mean age was 66.2 +/- 11.4; 60.6% were men; mean body mass index (BMI) 24.9 +/- 3.4 kg/m(2)). MEASUREMENTS: Hypertension was defined as systolic BP > or =140 mmHg and/or diastolic BP > or =90 mmHg and/or antihypertensive drug treatment. Leptin was measured by radioimmunoassay. RESULTS: After an average 4.4-year follow-up (minimum 2-maximum 7 years), 106 (17.6%) new cases of hypertension were identified. At baseline, participants who developed hypertension were older and had higher systolic BP and higher total cholesterol compared to participants who remained normotensive. Baseline serum leptin levels were higher in participants who developed hypertension compared to persistent normotensives [median (25th-75th range)] [8.8(5-16) vs 7(4-11) ng/ml, P = 0.002]. In logistic regression models, leptin (log-transformed) predicted incident hypertension before and after adjustments for baseline age, BMI, systolic BP, total cholesterol, medications, and previous cardiovascular disease (OR 1.75 95% CI 1.17-2.61, P = 0.006). This association persisted after exclusion of 45 obese participants. CONCLUSION: Higher leptin levels were independently associated with increased odds of incident hypertension in older adults.

High-density lipoprotein subclasses are a potential intermediary between alcohol intake and reduced risk of cardiovascular disease: the Rancho Bernardo Study.

We conducted a cross-sectional study of NMR-derived HDL subclasses and alcohol intake among 2171 community-dwelling older adults with a large proportion of daily or near-daily alcohol consumers (44 %). We aimed to assess whether, in addition to increasing total HDL, alcohol may induce a beneficial shift in HDL particle size distribution. Participants were categorised based on reported alcohol intake (g per week) and on frequency (none, < 3 times/week, 3-4 times/week, ≥ 5 times/week). The association between alcohol intake and lipoprotein fractions was examined using sex-specific linear regression models adjusted for age, BMI, diabetes, current smoking, exercise and hormone therapy in women. There was a stepwise gradient with the highest weekly alcohol consumption associated with the highest total HDL size and greatest number of medium and large HDL particles, as well as higher total HDL concentrations (all P < 0.001); total small HDL did not differ. Alcohol-HDL size associations were similar in both sexes and did not differ by use of hormone replacement therapy in women. In conclusion, regular alcohol consumers had a higher number and percentage of large HDL particles than non-drinkers. These results suggest that one way that alcohol may decrease CVD is through potentially favourable changes in lipoprotein subclass composition.

Sex and age differences in the association of obesity and smoking with hypertension and type 2 diabetes in Southern California American Indians, 2002-2006.

OBJECTIVE: Assess age and sex differences in the association of obesity and smoking with diabetes and hypertension and report the prevalence of these cardiovascular disease (CVD) risk factors in Southern California American Indian/Alaska Native (AlAN) adults. DESIGN: Cross-sectional study. SETTING: Visit data from 2002-2006 were extracted from one Southern California AlAN health clinic system. PARTICIPANTS: 10,351 AIAN adults visiting the health clinic system. MAIN OUTCOME MEASURES: Odds ratios were examined to assess the association of obesity and smoking with diabetes and hypertension and prevalence rates for obesity, smoking, diabetes, and hypertension were reported. RESULTS: Obesity (women: 53%, men: 55%), smoking (women: 16%, men: 18%), diabetes (women: 14%, men: 16%), and hypertension (women: 32%, men: 37%) were very prevalent. For women aged -35 years, increasing obesity was significantly associated with diabetes. For men aged -25 years, morbid obesity and smoking were significantly associated with diabetes for many age groups. Increasing overweight/obesity and smoking were associated with hypertension among adults aged 18-65 years. CONCLUSIONS: Southern California AIANs had higher obesity, diabetes, and hypertension prevalence than the general Southern California population, and higher obesity prevalence compared to other AIANs. Highly prevalent risk factors create a great burden, as CVD is the leading cause of death among AIAN adults. AIANs are diverse and need interventions tailored to cultural customs and health problems most prevalent in each tribal community.

Obesity and other cardiovascular disease risk factors and their association with osteoarthritis in Southern California American Indians, 2002-2006.

OBJECTIVE: Assess age and sex differences in the association of obesity and other CVD risk factors with osteoarthritis (OA) in Southern California American Indian/Alaska Native (AIAN) adults. DESIGN: Cross-sectional study. SETTING: Southern California. PARTICIPANTS: 6,299 AIAN adults aged 35+ years from health clinic system. MAIN OUTCOME MEASURES: Osteoarthritis prevalence. RESULTS: Age-adjusted OA prevalence was 16.5% in women and 11.5% in men. OA prevalence increased with age and was higher in women. Very and morbid levels of obesity were associated with higher OA prevalence in some age groups. Hypertension was strongly associated with increased OA and current smoking tended to be associated with increased OA. For men, we found no association between diabetes and OA; however, diabetes was associated with more OA for women aged 35-54 years. CONCLUSIONS: Southern California AIANs may have lower OA prevalence than the US population as a whole. Comparisons of OA prevalence with other AIAN communities were not possible due to lack of other similar published results. Further studies are needed to determine the impact of OA within this understudied minority population.

Usefulness of microalbuminuria versus the metabolic syndrome as a predictor of cardiovascular disease in women and men>40 years of age (from the Rancho Bernardo Study).

To examine the sex-specific contributions of the metabolic syndrome and microalbuminuria to cardiovascular disease (CVD) and coronary heart disease (CHD) mortality in community-dwelling older adults, 869 women and 575 men aged 40 to 96 years (mean age 71) completed questionnaires, physical examinations, and fasting laboratory tests between 1992 and 1995. Participants were followed over an average of 8 years. CVD and CHD mortality were analyzed using Cox proportional hazards models. At baseline, 267 participants had the Adult Treatment Panel III metabolic syndrome, 151 had microalbuminuria, and 34 had both. During follow-up, there were 180 CVD deaths, including 83 CHD deaths. In women, microalbuminuria was associated with a twofold increased risk of CVD and CHD mortality (p

Measures of renal function, BMD, bone loss, and osteoporotic fracture in older adults: the Rancho Bernardo study.

UNLABELLED: The association between bone and renal function in healthy seniors is not well studied. In this cross-sectional and longitudinal study in 1713 older men and women, creatinine clearance was significantly associated with hip BMD. If confirmed, this may warrant adding mild to moderate renal dysfunction as an indication for osteoporosis screening. INTRODUCTION: This study determined the cross-sectional and longitudinal association between measures of renal function and BMD, bone loss, and osteoporotic fracture in older adults. It determined which measure of renal function--creatinine clearance by the Cockcroft-Gault (CG) equation, estimated glomerular filtration rate by the Modification of Diet in Renal Disease (MDRD) equation, or serum creatinine--is most strongly associated with BMD and osteoporotic fracture. MATERIALS AND METHODS: This was a cross-sectional and prospective study in older community-dwelling men and women. Between 1992 and 1995, 1713 participants (average age, 71.3 +/- 11.1 years) completed standardized questionnaires, physical examinations, laboratory testing, and bone densitometry; 1023 participants returned for a follow-up visit in 1997-1999, an average of 4.1 +/- 0.9 years later. RESULTS: Calculated renal function declined with age (p < 0.001). Renal function was categorized by Kidney Disease Outcomes Quality Initiative (K/DOQI) chronic kidney disease (CKD) stage. By the CG equation, at baseline, 5.5% of participants had stage 1 CKD (glomerular filtration rate > or = 90 ml/min/1.73 m(2)), 43.0% had stage 2 CKD (60-89 ml/min/1.73 m(2)), 48.8% had stage 3 CKD (30-59 ml/min/1.73 m(2)), and 2.7% had stages 4 and 5 CKD (<30 ml/min/1.73 m(2)). Using the MDRD equation, these percents were 7.0%, 61.7%, 30.9%, and 0.5%, respectively. In cross-sectional analyses, there was a significant linear association between creatinine clearance by CG or glomerular filtration rate by MDRD and hip BMD. In prospective analyses, there was an average annual bone loss of 0.6% and a significant association between baseline CG and 4-year hip bone loss. There was no association between baseline MDRD or serum creatinine and bone loss. At baseline, 180 of 1713 participants (11%) reported at least one clinical fracture of the hip, femur, forearm, or wrist; 79 (8%) reported new clinical fractures during follow-up. Baseline renal function by any measure was not significantly associated with prevalent or incident clinical fractures. CONCLUSIONS: Although renal function measured by both CG and MDRD was associated with BMD in cross-sectional analyses, only creatinine clearance by CG predicted 4-year bone loss. If confirmed, this should be the preferred method for assessing the association between renal function and BMD. Cross-sectional associations between renal function and BMD were strongest at higher CKD stage. None of the baseline renal function estimates was associated with prevalent or incident fractures, perhaps reflecting the multifactorial etiology of fractures beyond BMD. If further studies in the elderly confirm renal function as an important predictor of bone loss and fracture, this may warrant adding mild to moderate renal dysfunction as an indication for osteoporosis screening.

Is radiographic vertebral fracture a risk factor for mortality?

Clinical fractures predict increased mortality risk, but few studies report mortality based on prevalent radiographically defined vertebral fracture. This study examined whether radiographically defined vertebral fracture is a risk factor for mortality in older adults. The 1,580 participants in California (631 men, 949 women) were aged > or =50 years in 1992-1996. Lateral spine radiographs, and information about medical history and behaviors, were obtained. Overall, 55 (8.7%) men and 123 (13%) women had at least one prevalent fracture at baseline; of these, 48 women and 14 men had two or more. Over 7.6 years, 460 participants died, 27.6% without and 41.0% with prevalent fractures (p < 0.001). Prevalent vertebral fracture was not associated with all-cause mortality in both sexes combined (adjusted hazard ratio = 1.09, 95% confidence interval: 0.84, 1.42) or sex-specific analyses (women: adjusted hazard ratio = 1.15, 95% confidence interval: 0.83, 1.59; men: adjusted hazard ratio = 0.89, 95% confidence interval: 0.55, 1.46). However, women with two or more prevalent fractures had increased risk of all-cause mortality (adjusted hazard ratio = 1.56, 95% confidence interval: 1.01, 2.40; p = 0.04). Women with any prevalent vertebral fractures also had increased mortality risk from "other" causes (adjusted hazard ratio = 1.59, 95% confidence interval: 1.03, 2.45; p = 0.04) but not cardiovascular disease or cancer. A single radiographic vertebral fracture is not a risk for mortality in older women; larger, longer studies of men and those with two or more radiographic vertebral fractures are needed.

Searching for polycystic ovary syndrome in postmenopausal women: evidence of a dose-effect association with prevalent cardiovascular disease.

OBJECTIVE: To test the hypothesis that polycystic ovary syndrome (PCOS) is associated with an increased risk of atherosclerotic cardiovascular disease (CVD) in older postmenopausal women. DESIGN: Cross-sectional study of community-dwelling non-estrogen-using postmenopausal-white women (N=713; mean+/-SD age, 73.8+/-7.9 years; mean body mass index, 24.0+/-3.5 kg/m) participating in the Rancho Bernardo Study. A putative PCOS phenotype was defined as the presence of three or more of the following features: (1) recalled history of irregular menses, (2) symptomatic premenopausal hyperandrogenism or biochemical evidence of current biochemical hyperandrogenism, (3) history of infertility or miscarriage, (4) central obesity, or (5) insulin resistance. Atherosclerotic CVD was determined from clinical history, electrocardiography, and structured interviews using validated techniques. The analysis was stratified by diabetes status, ascertained from medical history or 75-g oral glucose tolerance tests. RESULTS: The PCOS phenotype was present in 9.3% of the entire cohort and 5.8% of nondiabetic women. The prevalence of CVD was similar between women with the phenotype and unaffected women (27.3% vs 24.4%). Among women with intact ovaries and no diabetes, there was a stepwise graded association between an increasing number of features of the PCOS phenotype (ie, none to three or more) and prevalent CVD (P=0.02). A similar association was also observed for coronary heart disease alone (P=0.03). CONCLUSIONS: Among nondiabetic postmenopausal women with intact ovaries, prevalent atherosclerotic CVD is associated with features of a putative PCOS phenotype. This finding supports the thesis that PCOS increases the risk of atherosclerotic CVD after menopause.

The Dehydroepiandrosterone And WellNess (DAWN) study: research design and methods.

Levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), the major secretory products of the adrenal gland, decline dramatically with age, concurrent with the onset of degenerative changes and chronic diseases associated with aging. Epidemiological evidences in humans and animal studies suggest that DHEA(S) may have cardioprotective, antiobesity, antidiabetic, and immuno-enhancing properties. These observations led to the proposal that restoration of DHEA to young adult levels may have beneficial effects on age-related conditions. Most clinical trials of DHEA replacement have been limited due to small samples and short duration, restriction to one sex, failure to adjust for baseline endogenous hormone level and age, or lack of placebo comparison groups. We designed a double blind, placebo-controlled randomized trial to determine the acceptability, benefits, and adverse effects of 50 mg daily oral DHEA replacement for one year in 110 men and 115 women, aged 55 to 85, who were healthy and not currently using hormone therapy. A wide range of biological outcomes were studied including bone mineral density and metabolism, body composition and muscle strength, immune function, and cardiovascular risk factors. Steroid hormone levels, bone markers, cytokines, and the IGF-I, IGF binding protein system were measured at baseline and at 3 follow-up clinic visits. Changes in mood and well-being, cognitive function, and sexuality were assessed. Information on potentially confounding covariates such as smoking, alcohol consumption, exercise, diet and dietary supplements were obtained, and potential adverse effects of DHEA administration were monitored. This study enables an examination of the benefits of DHEA administration on the health of older men and women, and the influence of gender, age, and baseline endogenous DHEA level on each outcome variable. Potential mechanisms of DHEA action, including the biotransformation of DHEA to active steroids and steroid metabolites, enhancement of IGF-I bioavailability, and inhibition of IL-6 production can also be evaluated.

Leptin predicts BMD and bone resorption in older women but not older men: the Rancho Bernardo study.

UNLABELLED: We studied the relation of leptin to bone, bone loss, and bone turnover in community-dwelling men and women. Leptin predicted higher BMD and lower bone turnover only in women. Leptin was not associated with 4-year bone loss in either sex. INTRODUCTION: Leptin, the protein product of the obesity (OB) gene produced in fat tissue, was originally thought to be involved only in the regulation of food intake and energy balance. Recent evidence suggests that leptin may play a role in the pathophysiology of several chronic diseases. Studies of the association between leptin and bone have been numerous yet inconclusive. Only one previous longitudinal study has been reported, which showed no association of leptin with BMD after adjusting for body size. MATERIALS AND METHODS: We report the association of serum leptin with BMD at the hip, spine, and midshaft radius in community-dwelling men (n = 498) and nonestrogen-using postmenopausal women (n = 411) 45-92 years of age. Serum leptin was measured in blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA; at the same visit, height, weight, and body fat (by bioelectrical impedance analysis) were measured, and bone resorption was assessed in a subset of men (n = 286) and women (n = 241) using urine N-telopeptide (NTX). Four years later, axial BMD was remeasured in 536 participants. Sex-specific associations of leptin with BMD, NTX, and bone loss were tested using regression analysis. RESULTS: In unadjusted analyses, leptin was associated with BMD at the femoral neck, total hip, lumbar spine, and midshaft radius in both sexes (p < 0.01). In multiple regression analyses, adjusted for age, BMI, and other bone-related factors, only women showed a graded stepwise positive association between serum leptin and BMD at all sites and a negative stepwise association with NTX (all p for trend < 0.01). Baseline leptin levels did not predict 4-year bone loss in either sex. CONCLUSIONS: A favorable dose-dependent leptin-BMD association unexplained by obesity was observed only in women. The reason for the sex difference is unknown.

Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study.

BACKGROUND: Several lines of evidence suggest that n-3 fatty acids reduce the risk of some chronic diseases, including heart disease, diabetes, and cancer. Other research, mainly in animals, also suggests a role in bone health. OBJECTIVE: We aimed to investigate the association between the ratio of dietary n-6 to n-3 fatty acids and bone mineral density (BMD) in 1532 community-dwelling men and women aged 45-90 y. DESIGN: Between 1988 and 1992, dietary data were obtained through self-administered food-frequency questionnaires, and BMD was measured at the hip and spine with the use of dual-energy X-ray absorptiometry. A medical history was obtained and current medication use was validated. Age- and multiple-adjusted linear regression analyses were performed. RESULTS: There was a significant inverse association between the ratio of dietary linoleic acid to alpha-linolenic acid and BMD at the hip in 642 men, 564 women not using hormone therapy, and 326 women using hormone therapy; these results were independent of age, body mass index, and lifestyle factors. An increasing ratio of total dietary n-6 to n-3 fatty acids was also significantly and independently associated with lower BMD at the hip in all women and at the spine in women not using hormone therapy. CONCLUSIONS: A higher ratio of n-6 to n-3 fatty acids is associated with lower BMD at the hip in both sexes. These findings suggest that the relative amounts of dietary polyunsaturated fatty acids may play a vital role in preserving skeletal integrity in older age.

Modification of the effects of estrogen therapy on HDL cholesterol levels by polymorphisms of the HDL-C receptor, SR-BI: the Rancho Bernardo Study.

BACKGROUND: Previous studies have found polymorphisms of the HDL receptor, SR-BI, to be associated with plasma HDL-C in women, but not men, suggesting a modifying role of estrogen. We examined whether the association between SR-BI genotypes and HDL-C is modified by use of unopposed estrogen in community-dwelling postmenopausal Caucasian women. METHODS: Common polymorphisms in Intron5 and Exon8 of the SR-BI gene were evaluated in 689 women from the Rancho Bernardo Study. Multiple linear regression analysis was carried out adjusting for confounders. RESULTS: HDL-C levels did not differ significantly by genotype in the aggregate population. However, significant interaction was found between estrogen use and Exon8 (p=0.03), Intron5 (p=0.03) and Intron5/Exon8 diplotypes (p=0.01). SR-BI genotype was associated with HDL-C levels only among estrogen users (p=0.05) and explained 5.3% of the variance in HDL-C in this group. Consistent with prior studies, individuals heterozygous at both Intron5 and Exon8 loci had the lowest HDL-C levels. Among women with symptomatic CHD, the interaction between estrogen use and SR-BI genotype became even stronger. CONCLUSIONS: The effect that unopposed estrogen use has on HDL-C may depend on a woman's SR-BI genotype.

Apolipoprotein E genotype and response of lipid levels to postmenopausal estrogen use.

The allelic variation of Apolipoprotein E (ApoE) influences serum lipid levels. Postmenopausal estrogen replacement therapy (ERT) has favorable effects on the serum lipid profile. We examined the effect of ApoE genotype on lipid response to ERT in 692 community-dwelling women aged 60 and older. ApoE genotypes were categorized into three groups: ApoE 2 (E2/E2+E2/E3, n=94), ApoE 3 (E3/E3, n=430), and ApoE 4 (E3/E4+E4/E4, n=142). Compared to 497 women not using ERT, 169 women currently using ERT were younger (P=0.01), had lower levels of total cholesterol (TC; P=0.10) and low-density lipoprotein (P<0.001), higher levels of high-density lipoprotein (HDL; P<0.001) and triglycerides (TG; P=0.009), and were more likely to have had a surgical menopause (P<0.001). No significant differences in body mass index, alcohol intake, physical activity, or cigarette smoking were found between current ERT users and nonusers (P>0.10). There was a significant interaction between ApoE 2 and ERT for HDL levels: women with ApoE 2 using ERT had the highest HDL levels, and women with ApoE 2 not using ERT had the lowest HDL levels (P=0.015). The unfavorable effect of ApoE 4 genotype on lipoproteins is not altered by HRT, but ApoE 2 genotype modulates the HDL-ERT association in older women.

Sex and time differences in the associations of non-high-density lipoprotein cholesterol versus other lipid and lipoprotein factors in the prediction of cardiovascular death (The Rancho Bernardo Study).

Non-high-density lipoprotein (HDL) cholesterol (total cholesterol [TC] minus HDL cholesterol) has been suggested as the preferred lipid fraction to predict cardiovascular disease. We compared the ability of lipids, lipoproteins, the ratio of total to HDL cholesterol (TC/HDL), and non-HDL cholesterol to predict fatal coronary heart disease (CHD) and cardiovascular disease in 1,386 women and 1,094 men (mean age 69 years). After 10 years, there were more deaths in men (n = 310) than women (n = 268), but the proportions of deaths attributed to CHD (23% and 25%, respectively) and cardiovascular disease (48% and 47%) were similar. In men, age-adjusted values for non-HDL cholesterol, TC/HDL ratio, and triglycerides each predicted a significantly increased risk of CHD and cardiovascular disease; none of these associations was independent of pack-years of smoking, systolic blood pressure, fasting plasma glucose, body mass index, and physical activity. In women, age-adjusted non-HDL cholesterol levels did not predict CHD or cardiovascular disease events before or after adjusting for these covariates and for estrogen replacement therapy. In women, only the ratio of TC to HDL cholesterol predicted CHD and cardiovascular disease deaths independent of estrogen use and other risk factors. Observed associations were sensitive to time, being evident in women at 3 and 5 years, and lost thereafter, but not apparent before 10 years in men. Thus, non-HDL cholesterol is not superior to individual lipids, lipoproteins, or their ratios in the prediction of cardiovascular death in older adults.

Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study.

OBJECTIVE: To test the hypothesis that lower endogenous testosterone levels are associated with higher blood pressure, left ventricular mass, and left ventricular hypertrophy. DESIGN: Population-based cross-sectional study. METHODS: Sex hormone levels, measured by immunoassay, anthropometric measurements and resting blood pressure were studied in 1548 men aged 25-84 Years; echocardiography was completed in 1264 of these men. Partial correlations and multiple regressions were used to estimate the associations between sex hormones, blood pressure and left ventricular mass by height. Analyses of variance and covariance were used to compare men with categorical hypertension and left ventricular hypertrophy. RESULTS: In age-adjusted partial correlations, total testosterone and sex hormone-binding globulin (SHBG) were each inversely associated with systolic blood pressure (SBP) (P<0.001). Men with categorical hypertension (SBP> or =140 or diastolic blood pressure (DBP)> or =90 mmHg) had lower levels of total and free testosterone and SHBG before (P<0.001, P=0.011 and P<0.001, respectively) and after (P<0.001, P=0.035 and P=0.002, respectively) adjusting for body mass index (BMI). Total testosterone and SHBG were each inversely associated with left ventricular mass (P<0.001), and men with left ventricular hypertrophy had significantly lower levels of total testosterone (P=0.042) and SHBG (P=0.006); these associations were no longer significant after adjusting for BMI. CONCLUSION: The results of the present study are consistent with the hypothesis that lower levels of testosterone in men are associated with higher blood pressure, left ventricular mass, and left ventricular hypertrophy. The reduced associations after adjusting for BMI suggest that the association of low testosterone levels with blood pressure and left ventricular mass is mediated by obesity.

Isoflavones and cognitive function in older women: the SOy and Postmenopausal Health In Aging (SOPHIA) Study.

OBJECTIVE: This study examines the effects of a dietary supplement of isoflavones on cognitive function in postmenopausal women. DESIGN: Participants for this 6-month, double-blind, randomized, placebo-controlled clinical trial were women who were in good health, were postmenopausal at least 2 years, and were not using estrogen replacement therapy. Between July 24, 2000, and October 31, 2000, 56 women aged 55 to 74 years were randomized; 2 in the placebo group and 1 in the active treatment group did not complete the 6-month evaluation, and none withdrew because of adverse effects. Women randomized to active treatment (n = 27) took two pills per day, each containing 55 mg of soy-extracted isoflavones (110 mg total isoflavones per day; Healthy Woman: Soy Menopause Supplement, Personal Products Company, McNeil-PPC Inc., Skillman, NJ, USA). Women assigned to placebo (n = 26) took two identical-appearing pills per day containing inert ingredients. Cognitive function tests administered at baseline and follow-up included the following: Trails A and B, category fluency, and logical memory and recall (a paragraph recall test assessing immediate and delayed verbal memory). RESULTS: At baseline, all women were cognitively intact; there were no significant differences by treatment assignment in age, education, depressed mood, or cognitive function (all P values > 0.10). Compliance was 98% and 97%, respectively, in the placebo and treatment groups; all women took at least 85% of their pills. The women in the treatment group did consistently better, both as compared with their own baseline scores and as compared with the placebo group responses at 6 months. Comparisons of percentage change in cognitive function between baseline and follow-up showed greater improvement in category fluency for women on active treatment as compared with the case of those on placebo (P = 0.02) and showed (nonsignificantly) greater improvement on the two other tests of verbal memory and Trails B. CONCLUSION: These results suggest that isoflavone supplementation has a favorable effect on cognitive function, particularly verbal memory, in postmenopausal women.

Hysterectomy and oophorectomy are unrelated to bone loss in older women.

OBJECTIVE: The relation of hysterectomy and oophorectomy to change in bone mineral density (BMD) was examined in older women using and not using estrogen replacement therapy (ERT). METHODS: Women aged 60-80 years from the Rancho Bernardo Study attended clinic visits in 1988-1991 and 1992-1995 when hysterectomy and oophorectomy were ascertained, ERT use was validated and spine and hip BMD was assessed at both visits with DEXA. Women were either current ERT users or nonusers at both visits. RESULTS: Among these 447 women, average age was 71 (S.D.=9.0); average years postmenopause was 24.7 (S.D.=10.9). Overall, 122 had a hysterectomy with ovarian conservation and 91 had a hysterectomy with bilateral oophorectomy; 41% reported current ERT use for an average duration of 19.1 years (S.D.=10.8). Hysterectomized women were 2.3 times more likely to report ERT use than intact women (P<0.001). Comparisons adjusted for age, obesity, and age at menopause but not for ERT use showed hysterectomized women had less bone loss per year at the hip than intact women (P<0.05). However, this difference was explained by ERT; after adjustment for ERT, mean hip bone loss per year was -0.57% for intact women, -0.42% for hysterectomized women with ovarian conservation and -0.32% for bilaterally oophorectomized women (P's>0.10). There were no differences by hysterectomy or oophorectomy in bone loss at the spine or femoral neck. For all sites, women using ERT had higher BMD at both visits than nonusers (P's<0.001). Stratification by ERT showed that within users and nonusers, there were no differences in BMD or bone loss at any site by hysterectomy or oophorectomy. CONCLUSIONS: There are no long term effects of hysterectomy and bilateral oophorectomy on bone loss. Women who use ERT have better BMD than nonusers.

Adipocytokine profiles in a putative novel postmenopausal polycystic ovary syndrome (PCOS) phenotype parallel those in premenopausal PCOS: the Rancho Bernardo Study.

The objective was to investigate whether the associations between leptin, adiponectin, andadiposity reported in classic polycystic ovary syndrome (PCOS) are also observed in elderly women with a novel putative postmenopausal PCOS phenotype. We studied 713 postmenopausal community-dwelling women. Diagnosis of the novel phenotype required the presence of ≥3 diagnostic features including: 1) a personal history of oligomenorrhea; 2) history of infertility or miscarriage; 3) current or past clinical or hormonal evidence of hyperandrogenism; 4) central obesity; 5) biochemical evidence of insulin resistance. Women in the control group had ≤2 of these components. Mean age (±SD) was 74±8 years for the study cohort. Sixty-six women (9.3%) had the putative PCOS phenotype. Serum leptin was higher (mean 25.70±15.67 vs 14.94+9.89 ng/mL, P<.01) and adiponectin lower (mean 11.72±4.80 vs 17.31±7.45 µg/mL, P<.01) in cases vs controls. Leptin was positively, and adiponectin inversely, associated with an increasing number of phenotype features (P<.01 for linearity). In age-adjusted regression analysis, adjustment for waist circumference eliminated the association between leptin and the PCOS phenotype, but not the association between adiponectin and the PCOS phenotype. In this novel postmenopausal PCOS phenotype, adipocytokine profiles and their associations with adiposity parallel those reported in younger women with classic PCOS. These results support our hypothesis that a putative phenotype analogous to PCOS can be identified in postmenopausal women using clinical and biochemical criteria. Use of this novel phenotype could provide a basis for studies of the delayed consequences of PCOS in older women.